Effects of Adolescent Social Isolation on PFC's β-Catenin Levels and Anxiety-Like Behaviors in Male and Female Rats: Study of the Role of Dopaminergic D2 Receptors.

Adolescence is a key period of development when major cognitive and neurobiological changes occur. Results from our lab showed that 5 days of social isolation in adolescent rats led to molecular changes in the Wnt/β-catenin pathway and to higher cocaine responses during adulthood. We assessed whether 5 days of social isolation (SI) during adolescence would impact on β-catenin levels in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) as well as on anxiety-like behaviors in a sex- and time-dependent manner. We also investigated the role of dopaminergic neurotransmission on that impact, by using repeated administration of a D2 antagonist. Male and female Wistar rats were socially isolated between postnatal day (PND)30 to 35 or kept in their home cages (non-isolated), while they were treated with sulpiride (100 mg/kg, ip) or vehicle. Anxiety-like behaviors and exploratory activity were estimated by the open field test at 24 h (PND36) or 9 days (PND44) after isolation. Then, they were euthanized at PND36 or PND45, and β-catenin levels were analyzed by Western blot in PFC and NAcc. Our findings show that a brief SI during adolescence leads to a long-term impact on both β-catenin levels (10 days, PND45) and anxiety-like behaviors (9 days, PND44) with a significant increase and decrease, respectively, in female rats. In contrast, male rats show a rapid decrease in β-catenin levels in the PFC with no changes in anxiety-like behaviors (24 h, PND36). These suggest that adolescent SI induces mostly long-term changes in female while short term changes in male rats. Moreover, these changes seem to be modulated by dopaminergic neurotransmission since a sulpiride treatment during isolation prevented them.